铜死亡相关基因 CDK1 和 COA6 参与肝癌预后预测。
Cuproptosis-Related Genes CDK1 and COA6 Involved in the Prognosis Prediction of Liver Hepatocellular Carcinoma.
机构信息
Central Laboratory, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, China.
Department of Oncology, Minhang Hospital, Fudan University, China.
出版信息
Dis Markers. 2023 May 11;2023:5552798. doi: 10.1155/2023/5552798. eCollection 2023.
BACKGROUND
Liver hepatocellular carcinoma (LIHC) is the most frequently seen type of primary liver cancer. Cuproptosis is a novel form of cell death highly associated with mitochondrial metabolism. However, the clinical impact and pertinent mechanism of cuproptosis genes in LIHC remain largely unknown.
METHODS
From public databases, we systematically assessed common genes from LIHC differentially expressed genes (DEGs) and cuproptosis-related genes using bioinformatics analysis. These common genes were then analyzed by enrichment analysis, mutation analysis, risk score model, and others to find candidate hub genes related to LIHC and cuproptosis. Next, hub genes were determined by expression, clinical factors, immunoassay, and prognostic nomogram.
RESULTS
Based on 129 cuproptosis-related genes and 3492 LIHC DEGs, we totally identified 21 downregulated and 18 upregulated common genes, and they were enriched in pathways, such as zinc ion homeostasis and oxidative phosphorylation. In the mutation analysis, missense mutation was the most common type in LIHC patients, and the common gene F5 had the highest mutation frequency. After LASSO-Cox regression analysis and prognostic analysis, CDK1, ABCB6, LCAT, and COA6 were identified as prognostic signature genes. Among them, ABCB6 and LCAT were lowly expressed in tumors, and CDK1 and COA6 were highly expressed in tumors. In addition, ABCB6 and LCAT were negatively correlated with 6 kinds of immune cells, while CDK1 and COA6 were positively correlated with them. CDK1 and COA6 were identified as hub genes related to LIHC by Cox regression analysis and prognostic nomogram.
CONCLUSION
CDK1 and COA6 are two oncogenes in LIHC, which are involved in the molecular mechanism of cuproptosis and LIHC. Besides, CDK1 and COA6 can positively regulate the expressions of immune cells in LIHC. In clinical practice, they can be used as immunotherapeutic targets and prognostic predictors in LIHC, which sheds new light on the scientific fields of cuproptosis and LIHC.
背景
肝细胞肝癌（LIHC）是最常见的原发性肝癌类型。铜死亡是一种与线粒体代谢高度相关的新型细胞死亡形式。然而，LIHC 中铜死亡基因的临床影响和相关机制在很大程度上仍然未知。
方法
我们从公共数据库中系统地评估了 LIHC 差异表达基因（DEGs）和铜死亡相关基因的常见基因，使用生物信息学分析。然后，通过富集分析、突变分析、风险评分模型等对这些常见基因进行分析，以找到与 LIHC 和铜死亡相关的候选关键基因。接下来，通过表达、临床因素、免疫测定和预后列线图确定关键基因。
结果
基于 129 个铜死亡相关基因和 3492 个 LIHC DEGs，我们总共鉴定出 21 个下调和 18 个上调的常见基因，它们富集在锌离子稳态和氧化磷酸化等途径中。在突变分析中，错义突变是 LIHC 患者中最常见的类型，常见基因 F5 的突变频率最高。经过 LASSO-Cox 回归分析和预后分析，确定 CDK1、ABCB6、LCAT 和 COA6 为预后特征基因。其中，ABCB6 和 LCAT 在肿瘤中低表达，CDK1 和 COA6 在肿瘤中高表达。此外，ABCB6 和 LCAT 与 6 种免疫细胞呈负相关，而 CDK1 和 COA6 与它们呈正相关。通过 Cox 回归分析和预后列线图，CDK1 和 COA6 被确定为与 LIHC 相关的关键基因。
结论
CDK1 和 COA6 是 LIHC 中的两种癌基因，它们参与了铜死亡和 LIHC 的分子机制。此外，CDK1 和 COA6 可以正向调节 LIHC 中免疫细胞的表达。在临床实践中，它们可以作为 LIHC 的免疫治疗靶点和预后预测因子，为铜死亡和 LIHC 的科学领域提供了新的思路。
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